Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants.

Etesevimab in combination with JS026 neutralizing SARS-CoV-2 and its variants.
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DOI:
10.1080/22221751.2022.2032374
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发表时间:
2022-12
影响因子:
13.2
通讯作者:
Yan J
Yan J
中科院分区:
医学2区
文献类型:
--
作者:
Wang F;Li L;Dou Y;Shi R;Duan X;Liu H;Zhang J;Liu D;Wu J;He Y;Lan J;Lu B;Feng H;Yan J

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中和抗体是一种潜在的治疗方法,用于正在进行的COVID-19大流行。作为一种抗病毒药物,许多单克隆抗体识别SARS-CoV-2-RBD中与ACE 2结合位点重叠的表位。一些研究表明,刺突蛋白上的残留变化可显著降低中和抗体的效率。为了解决这个问题,治疗鸡尾酒可能是一个有效的对策。在本研究中,我们从一名康复期患者中分离出一种完全人源性中和抗体JS 026。比较分析显示,JS 026与SARS-CoV-2-RBD的结合主要位于2类和3类mAb的表位之间,而不是1类(etesevimab)抗体的表位。Etesevimab和JS 026的混合物增加了对野生型SARS-CoV-2和最近出现的α,β,γ和δ变体的中和效力。JS 026和鸡尾酒降低了hACE 2转基因小鼠感染肺中的病毒滴度,减轻了病理变化。这些发现将有利于基于抗体的治疗对策治疗COVID-19。
The neutralizing antibody is a potential therapeutic for the ongoing COVID-19 pandemic. As an antiviral agent, numerous mAbs recognize the epitopes that overlap with ACE2-binding sites in the SARS-CoV-2-RBD. Some studies have shown that residual changes on the spike protein can significantly decrease the efficiency of neutralizing antibodies. To address this issue, a therapeutic cocktail could be an effective countermeasure. In the present study, we isolated a fully human neutralizing antibody, JS026, from a convalescent patient. The comparative analysis revealed that JS026 binding to SARS-CoV-2-RBD mainly located between epitopes for class 2 and class 3 mAbs as opposed to that of class 1 (etesevimab) antibodies. A cocktail of etesevimab and JS026 increased neutralizing efficacy against both wild-type SARS-CoV-2 and the recent emergence of Alpha, Beta, Gamma, and Delta variants. JS026 and the cocktail reduced virus titers in the infected lungs of hACE2 transgenic mice and relieved pathological changes. These findings would benefit antibody-based therapeutic countermeasures in the treatment of COVID-19.
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